Health Effects of Calcium: Evidence From Mendelian Randomization Studies

Chen, Yiheng; Forgetta, Vincenzo; Richards, J. Brent; Zhou, Sirui

doi:10.1002/jbm4.10542

Cited by 9 publications

(3 citation statements)

References 90 publications

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“…(~0.1 mmol/L) was associated with a 25% increase in the risk of myocardial infarction (21), very similar to the effects found in the Bolland meta-analyses (19,20). Multiple other Mendelian randomisation studies have reproduced this finding (22). These findings are supported by a large body of observational data showing an association between serum calcium concentration and subsequent risk of cardiovascular events (23).…”

Section: Vitamin D and Calciumsupporting

confidence: 68%

EXTENSIVE EXPERTISE IN ENDOCRINOLOGY: Osteoporosis management

Reid

2022

European Journal of Endocrinology

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Fractures occur in about half of older white women, and almost a third of older white men. However, 80% of the older individuals who have fractures do not meet the bone density definition of osteoporosis, suggesting that this definition is not an appropriate threshold for offering treatment. Fracture risk can be estimated based on clinical risk factors with or without bone density. A combination of calculated risk, fracture history, and bone density is used in treatment decisions. Medications available for reducing fracture risk act either to inhibit bone resorption or to promote bone formation. Romosozumab is unique in that it has both activities. Bisphosphonates are the most widely used interventions because of their efficacy, safety and low cost. Continuous use of oral bisphosphonates for >5 years increases the risk of atypical femoral fractures, so is usually punctuated with drug holidays of 6-24 months. Denosumab is a further potent antiresorptive agent given as six-monthly subcutaneous injections. It is comparable to the bisphosphonates in efficacy and safety but has a rapid offset of effect after discontinuation so must be followed by an alternative drug, usually a bisphosphonate. Teriparatide stimulates both bone formation and resorption, substantially increases spine density and reduces vertebral and non-vertebral fracture rates, though data for hip fractures are scant. Treatment is usually limited to 18-24 months, followed by transition to an anti-resorptive. Romosozumab is given as monthly subcutaneous injections for one year, followed by an anti-resorptive. This sequence prevents more fractures than anti-resorptive therapy alone. Because of cost, anabolic drugs are usually reserved for those at very high fracture risk. 25-hydroxyvitamin D levels should be maintained above 30 nmol/L, using supplements if sunlight exposure is limited. Calcium intake has little effect on bone density and fracture risk but should be maintained above 500 mg/day using dietary sources.

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Section: Vitamin D and Calciumsupporting

confidence: 68%

EXTENSIVE EXPERTISE IN ENDOCRINOLOGY: Osteoporosis management

Reid

2022

European Journal of Endocrinology

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“…These findings are in line with recent Mendelian randomization studies. These studies take a genetic epidemiological approach to estimate causality and have suggested a positive causal influence of transient increases in serum calcium on increased cardiovascular disease risk, especially for myocardial infarction (MI) [20][21][22][23]. However, this increase in cardiovascular disease risk was not observed with higher intake of dietary calcium [24].…”

Section: Skeletal and Extraskeletal Effects Of Calcium And Vitamin Dmentioning

confidence: 99%

Cardiovascular Impact of Calcium and Vitamin D Supplements: A Narrative Review

et al. 2023

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Calcium and vitamin D play an important role in mineral homeostasis and the maintenance of skeletal health. Calcium and vitamin D supplements have been widely used for fracture prevention in elderly populations. Many trials have studied the effectiveness and cardiovascular safety of calcium and vitamin D supplementation, with disparate results. In this review, we summarize the most important trials and systematic reviews. There is significant heterogeneity in clinical trial design, differences in the nature of trial outcomes (self-reported vs. verified), prior calcium intake, and trial size. Inconsistent results have been reported concerning the effects of calcium and vitamin D supplementation on cardiovascular outcomes. Most current guidelines recommend calcium intake of up to 1,200 mg daily, preferably from the diet, without concern for cardiovascular risk. Recommendations regarding vitamin D supplementation vary widely. There is compelling evidence from well-conducted randomized trials that modest vitamin D supplementation is safe but does not confer cardiovascular benefit or cardiovascular harm.

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“…There is still uncertainty regarding the benefits of CaDs, although many studies have been conducted, including epidemiological studies, metaanalyses, and Mendelian randomization analyses [1,[13][14][15]. However, most studies included only Caucasians, who generally consume moderateto-high amounts of dietary calcium and have a relatively high body mass index (BMI), which potentially limits the generalizability of their results to other populations [4,16].…”

Section: Introductionmentioning

confidence: 99%